The role of Sprouty4 in development and cancer and functional consequences of Sprouty interacting with Caveolin-1

intracellular signaling pathways that ultimately determine cell fate. The coordinated action of both positive and negative modulators is essential for spatial and temporal control of these pathways to avoid developmental defects and malignant transformation. Sprouty (Spry) proteins are a family of ligand-induced regulators of RTK-mediated intracellular cascades. In mammals, there are four isoforms. Their activity targets signal transduction induced by various growth factors, suggesting that their activities have broad biological consequences. Spry proteins have the capacity to attenuate or potentiate different pathways depending on the Spry isoform, the growth factor and the cellular context. In this study I investigate the functional consequences of Spry interacting with Caveolin-1. I demonstrate that in the context of FGF2 and EGF signaling, Caveolin-1 differentially modulates the function of the four isoforms. This suggests that Caveolin-1 might contribute to the divergence among the four isoforms and, depending on its own expression pattern, could contribute to the cell context-dependency of Spry proteins. In a second part of my studies I assess the role of mSpry4 in murine pancreas development. Analyzing this organ for the presence of Spry proteins, I detect very specific expression of mSpry4 in one population of endocrine cells, namely in the α cells. In the pancreas, different endocrine cell types are organized within islets of Langerhans. The insulin-secreting β cells occupy the core of the islets and are surrounded by α, δ and PP cells, secreting glucagon, somatostatin and pancreatic polypeptide, respectively. Using a doxycycline-inducible transgenic system I conditionally express mSpry4 in the insulinproducing β cells and demonstrate that ectopic mSpry4 interferes with proper segregation of the endocrine cells. Employing the endocrine precursor cell line PANC-1 as an in vitro model for islet formation I find that mSpry4 inhibits migration and adhesion of these cells, probably by interfering with the localization PTP1B, a mediator of integrin signaling. Furthermore, the role of mSpry4 in tumorigenesis was assessed using the well established Rip1Tag2 mouse model. In these mice, transgenic expression of large T antigen results in β cell carcinogenesis. We find that expression of mSpry4 in β cells has a moderate effect on tumor formation. Experiments with isolated tumor cells imply that transformation of β cells by means of large T antigen results in constitutive activation of p42/44 ERK signaling by a mechanism that renders mSpry4 ineffective as an inhibitor of this pathway

Past Futures and the Rise of the Flexibilisation Imperative

Flexibility has developed into an important condition of society today and is often perceived as reaction to challenging social circumstances. But how and why did flexibility became so powerful on both the societal and individual level? And how, if the focus is on biographies, is it linked to education? In this nexus, education and institutionalised educational processes build a hinge between society and the individual. To find educational solutions to meet the challenge of the change in societies’ constitution, the future is addressed. This is particularly true for vocational education and training (VET), since VET is supposed to prepare for the working world of tomorrow and thus already has the anticipation of the future in its mandate. However, futures are always speculative and plural in many respects. Therefore, futures coexist or compete for validity and thereby exclude each other. Against this backdrop, the general research interest lies in the genesis of the contemporary, flexible human constitution and the influence of VET on its evolvement. The the question will be examined, as to how the flexibilisation of humans was discussed within future configurations of politicians and in the VET law since its establishment in 1930

The surfaces of the Moon and Mercury: an experimental and numerical approach to ion sputtering

Energetic solar wind ions erode the surfaces of the Moon and Mercury through sputtering. The process of sputtering ejects material with suprathermal velocities into the collisionless exospheres of their respective rocky body. The suprathermal populations in the exosphere thus directly sample the surface. Given the solar wind precipitation rates and areas, exospheric compositions can be interpreted if the sputtering yield of solar wind ions is known. A better understanding of ion sputtering will allow to quantify its importance relative to competing suprathermal processes such as photon stimulated desorption and micrometeoroid impact vaporization. In the context of this thesis, mineral analogues and regolith samples were prepared, irradiated, and analyzed. A new preparation method using a custom pellet die was developed to obtain exceptionally resilient mineral powder pellets, without the use of a binder or adhesives. The analysis included infrared measurements in the 7–14 μm range, covered by BepiColombo/MERTIS (2.5–15 μm). We conclude that the interaction volume of infrared radiation exceeds the depth amorphized by average-velocity solar wind ions and does not lead to reliably detectable shifts in the spectrum. The efficient and rapid amorphization of the upper layer was determined computationally, and supported experimentally in collaboration with Biber et al. [1]. Therein, a crystal lattice effect on the sputter yield could not be detected between mineral pellets with microscopically rough surfaces and the glassy thin films produced from the same mineral powder. The differences in sputter yields could be attributed to roughness effects, suggesting extensive amorphization of the powder pellet surface. The laboratory sputter yield results for flat surfaces were used to evaluate the established sputter code SDTrimSP and motivate the addition of two new models. The first model differentiates between oxide-bound elements and unbound elements in the sample and assigns density according to either the element or the oxide. It is capable of reliably reproducing mineral densities with simulated amorphization, causing only minor density changes at the surface that do not negatively affect the model. The second model expands on the commonly used surface binding energies by assigning a binding energy within the bulk sample. This bulk binding energy is based on the enthalpy of formation required to break up the oxides that make up the mineral. Both models rely solely on tabulated data and no parameter adjustment is necessary to fit laboratory data. The increased binding energies lead to a broadening of the energy distribution as observed in laboratory data of oxidized metal. At normal incidence, SRIM yields are up to a factor five above laboratory yields. SDTrimSP simulation results however are in unprecedented agreement with laboratory data when including the two newly implemented models. In a sputter-unrelated part of this thesis, Mercury’s earliest magma ocean and atmosphere were modeled. A special focus was put on the loss or accumulation of sodium over the magma ocean lifetime, in an attempt to explain the exceptionally high surface concentrations of moderately volatile elements such as sodium, potassium, sulfur, and chloride on Mercury. Under average ‘young-Sun space weather conditions’, the combined atmospheric loss from plasma heating, photoevaporation, Jeans escape, and photoionization only accounts for a ≤0.02% decrease of the total sodium present in the mantle. This low degree of loss supports formation models which are based on the accretion of primitive chondrites to explain contemporary Mercury observations. In conclusion, this thesis has advanced the understanding of sputtering on rock-forming minerals relevant for the Moon and Mercury. It includes data of lower than previously assumed yields, the ruling out of a crystal lattice effect on the sputter process, and the implementation of two new sputter simulation models, which in combination show results with unprecedented agreement with laboratory data. The laboratory data-verified computed sputter yields and their angular and energy distributions will help to differentiate solar wind ion sputtering from competing space weathering processes that provide suprathermal species to the exospheres of the Moon and Mercury

L’approche systémique :: une piste pour l’enseignant face aux représentations négatives de l’orthographe des élèves à l’entrée dans l’écrit

Cette étude qualitative a comme point de départ les paroles de ses participants qui sont sept élèves entre 7 et 9 ans qui suivent actuellement ou qui ont suivi le programme d’introduction (la 3ème année HarmoS sur deux ans). La problématique thématise les conséquences de la peur de la faute d’orthographe à l’entrée dans l’écrit. On tentera également de démontrer ce que l’approche systémique peut apporter à l’enseignant face à cette problématique. Dans cette recherche, cela se fera à travers une activité collective durant laquelle les élèves pourront exprimer leurs peurs, raconter leurs anecdotes ou donner des conseils à leurs camarades dans un cadre sécurisé. L’accent est mis sur les actions possibles de l’enseignant et les outils que l’approche systémique en milieu scolaire lui met à disposition